Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia.
Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia.
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PTPN2（蛋白酪氨酸磷酸酶非受体2型，也称为TC-PTP）是一种细胞质酪氨酸磷酸酶，作为多种酪氨酸激酶和其他信号蛋白的负调节因子。与其在免疫系统调节中的作用一致，PTPN2被确定为自身免疫性疾病的易感性位点。在这项工作中，我们描述了PTPN2在人t细胞急性淋巴细胞白血病（T-ALL）中的局灶性缺失的鉴定。PTPN2缺失在TLX1转录因子癌基因异常表达的t - all中被特异性发现，包括4例也表达NUP214-ABL1酪氨酸激酶的病例。抑制PTPN2表达增加T-ALL细胞的增殖和细胞因子敏感性。此外，PTPN2被鉴定为NUP214-ABL1激酶活性的负调节因子。我们的研究为PTPN2的肿瘤抑制作用提供了遗传和功能证据，并表明PTPN2的表达水平可能调节对治疗的反应。
PTPN2 (protein tyrosine phosphatase non-receptor type 2, also known as TC-PTP) is a cytosolic tyrosine phosphatase that functions as a negative regulator of a variety of tyrosine kinases and other signaling proteins. In agreement with its role in the regulation of the immune system, PTPN2 was identified as a susceptibility locus for autoimmune diseases. In this work, we describe the identification of focal deletions of PTPN2 in human T-cell acute lymphoblastic leukemia (T-ALL). Deletion of PTPN2 was specifically found in T-ALLs with aberrant expression of the TLX1 transcription factor oncogene, including four cases also expressing the NUP214-ABL1 tyrosine kinase. Knockdown of PTPN2 expression increased the proliferation and cytokine sensitivity of T-ALL cells. In addition, PTPN2 was identified as a negative regulator of NUP214-ABL1 kinase activity. Our study provides genetic and functional evidence for a tumor suppressor role of PTPN2, and suggests that expression levels of PTPN2 may modulate response to treatment.
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影响因子：
5.3
作者：
Lu, Xiaoqing;Chen, Jun;Lossos, Izidore S.
通讯作者：
Lossos, Izidore S.
DOI：
10.1084/jem.20042524
发表时间：
2005-06-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dik WA;Pike-Overzet K;Weerkamp F;de Ridder D;de Haas EF;Baert MR;van der Spek P;Koster EE;Reinders MJ;van Dongen JJ;Langerak AW;Staal FJ
通讯作者：
Staal FJ
影响因子：
20.3
作者：
De Keersmaecker, K;Graux, C;Cools, J
通讯作者：
Cools, J
影响因子：
50.3
作者：
Ferrando, AA;Neuberg, DS;Look, AT
通讯作者：
Look, AT
影响因子：
4.8
作者：
Tiganis, T;Flint, AJ;Tonks, NK
通讯作者：
Tonks, NK